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Activation of gelatinases by fibrin is PA/plasmin system-dependent in human glomerular endothelial cells

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Abstract

Evidence suggests that fibrin deposit is related to severity of glomerulonephropathy. Fibrin is considered to play an active role beyond a haemostatic plug or temporary matrix in response to injury. We have reported that fibrin induced specific morphological changes and up-regulated intercellular adhesion molecule-1 expression of glomerular endothelial cells (GECs). Changes of gelatinases activity have been implicated playing a prominent role in glomerular diseases involving matrix turnover. This study examined whether overlying fibrin influences the expression of gelatinase A and B in cultured human GECs and mechanism underlying the activation. No gelatinase activity was detectable in supernatant of cultured GECs; however, physiological concentration of fibrin (0.5–2.0 mg/ml) induced a dramatic expression of activated MMP-2 and MMP-9 at both mRNA and protein level in a dose and time dependent manner. Increased mRNA level of membrane-type 1 matrix metalloproteinases (MT1-MMPs) was also found. Interestingly, we observed that fibrin also induced the expression of tissue type plasminogen activator (tPA), urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 by casein zymographic and reverse zymographic analysis. Fibrin plate assay revealed the net activity was PA predominant. Serine protease inhibitor aprotinin blocked the conversion of pro-gelatinase A and B to their active forms. The results demonstrate that overlying fibrin increased the secretion of gelatinase A and B from GECs. PA/plasmin proteolytic pathways contributed to the activation of gelatinases.

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Authors and Affiliations

  1. Department of Nephrology, Kidney Center and Key Laboratory of PLA, General Hospital of PLA, 28 Fuxing Road, Beijing, 100853, P.R. China

    Guangyan Cai, Xiangmei Chen, Bo Fu & Yang Lu

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  1. Guangyan Cai
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  2. Xiangmei Chen
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  3. Bo Fu
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Correspondence to Xiangmei Chen.

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Cai, G., Chen, X., Fu, B. et al. Activation of gelatinases by fibrin is PA/plasmin system-dependent in human glomerular endothelial cells. Mol Cell Biochem 277, 171–179 (2005). https://doi.org/10.1007/s11010-005-5995-3

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  • DOI: https://doi.org/10.1007/s11010-005-5995-3

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